General Strategy for Direct Cytosolic Protein Delivery via Protein–Nanoparticle Co-engineering
2017; American Chemical Society; Volume: 11; Issue: 6 Linguagem: Inglês
10.1021/acsnano.7b02884
ISSN1936-086X
AutoresRubul Mout, Moumita Ray, Tristan Tay, Kanae Sasaki, Gülen Yesilbag Tonga, Vincent M. Rotello,
Tópico(s)Virus-based gene therapy research
ResumoEndosomal entrapment is a key hurdle for most intracellular protein-based therapeutic strategies. We report a general strategy for efficient delivery of proteins to the cytosol through co-engineering of proteins and nanoparticle vehicles. The proteins feature an oligo(glutamate) sequence (E-tag) that binds arginine-functionalized gold nanoparticles, generating hierarchical spherical nanoassemblies. These assemblies fuse with cell membranes, releasing the E-tagged protein directly into the cytosol. Five different proteins with diverse charges, sizes, and functions were effectively delivered into cells, demonstrating the generality of our method. Significantly, the engineered proteins retained activity after cytosolic delivery, as demonstrated through the delivery of active Cre recombinase, and granzyme A to kill cancer cells.
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